A comprehensive characterization of the central neural pathways influencing cardiovascular activity is fundamental to understanding the role of the nervous system in the etiology of certain forms of hypertension. This necessitates describing the spinal and supraspinal afferentation of the sympathetic preganglionic neurons (SPNs). The present application proposes a combination of neuroanatomical and neurophysiological studies directed toward this objective. Three series of investigations are proposed. The first involves a comprehensive anatomical and physiological examination of the serotonergic raphe-SPN pathway. Using autoradiography, horseradish peroxidase (HRP), lesion, microstimulation, and extracellular recording techniques, studies have been designed to: (a) localize the cells of origin and spinal trajectory of the raphe-SPN system; (b) establish the conduction velocities and degree of convergence and divergence of raphe axons terminating upon the SPNs; (c) investigate the spatial and temporal properties of the inhibition of SPN discharge associated with activation of this descending system; (d) assess the involvement of the raphe in baroreceptor and somatosympathetic reflexes; and (e) establish the role of the raphe in the "tonic" and "phasic" modulation of arterial blood pressure. The second involves anterograde transport studies to localize the cells of origin of the catecholaminergic input(s) upon the SPNs. Using autoradiography, the spinal projections of cells in the regions of the nuclei reticularis lateralis, locus coeruleus, and subcoeruleus would be described. Anterograde tract tracing would also be initiated on the paraventricular nucleus of the hypothalamus. The final project involves a preliminary electron microscopic description of the cytological characteristics of axon terminals on HRP-labelled preganglionic neurons. It is anticipated that the completion of these studies would provide a description of the serotonergic raphe-SPN pathway, would localize the catecholaminergic input (s) upon the SPNs, and would give preliminary data on the detailed morphology of synapses on SPNs.